AB1313 THE RATIONAL USE OF BIOLOGICS IN REFRACTORY IMMUNE-MEDIATED INFLAMMATORY DISEASES CONSORTIUM (RUBRIC) NATIONAL REGISTRY: RESULTS ON GLUCOCORTICOID USE AND WORK PRODUCTIVITY
Authors: A. Musters, M. Kleijn-de Graaf, S. Tas
Journal: Annals of the Rheumatic Diseases (2022)

Background Rare therapy-refractory immune-mediated inflammatory diseases (IMIDs) are increasingly treated with new targeted therapies such as biological (b) or targeted synthetic (ts) DMARDs. However, in the Dutch healthcare system these treatments are not reimbursed for off-label use unless there is sufficient evidence of efficacy. Currently, no official guidelines or treatment protocols exist for many of these rare diseases. To overcome this issue we set up a national registry to document off-label use of b/tsDMARDs in patients with rare therapy-refractory IMIDs and to document efficacy and safety of these therapies. Objectives To report results on glucocorticoid use and work productivity of patients with rare therapy-refractory IMIDs treated off-label with b/tsDMARDs. Methods Using the web-based RUBRIC registry patients with rare therapy-refractory IMIDs treated off-label with b/tsDMARDs were prospectively followed to document efficacy and safety. Physicians supplied data on disease activity (i.e. VAS physician and ESR/CRP) and concomitant medication, including glucocorticoid use. Patients filled out questionnaires on patient reported outcomes (PROs; i.e. HAQ, WPAI-GH, SF-36, PASS, EQ-5D) prior to starting off-label treatment and at regular intervals afterwards. Any potential serious adverse events were also recorded. Results Many different diagnosis-treatment combinations were recorded (i.e. undifferentiated vasculitis, TRAPS, Hyper-IgD syndrome, auto-inflammatory diseases treated with various b/tsDMARDs). Of the 82 patients currently followed in RUBRIC, for 61 patients multiple questionnaires over a time period of &gt; 1 year were available for analysis. Glucocorticoid use was documented accurately in 55 patients. Analysis of glucocorticoid use demonstrated that the majority of patients (38/55; 69.1%) used glucocorticoids prior to off-label treatment and all patients remained at a stable dose (10/55; 18.2%) or could reduce the dose (23/55; 41.8%), whereas (5/55; 9.1%) could eventually even stop glucocorticoids completely. Of the patients that did not use glucocorticoids prior to off-label b/tsDMARD therapy, no glucocorticoids were initiated. Analysis of WPAI-GH over time revealed that off-label treatment resulted in a significant gain in work productivity in all working patients and 15% of patients who were not employed prior to initiating off-label treatment were able to resume work again, whereas none of the patients became unemployed during off-label treatment. No serious adverse events associated with off-label b/tsDMARD therapy were reported. Conclusion Off-label treatment of rare therapy-refractory IMIDs with b/tsDMARDs results in a clear beneficial effect as glucocorticoid use could be reduced or stopped in the majority of patients and a clear increase in work productivity/employment was observed. Despite these positive outcomes, at present not enough patients per diagnosis-treatment combination have been included in the registry to draw definitive conclusions on efficacy and safety of specific off-label treatments or to formulate treatment recommendations for certain diseases. Consequently, it is important to continue the registry and include more patients or link various (inter)national registries to obtain sufficient data and promote evidence-based and effective use of biologics in rare therapy-refractory IMIDs. This may eventually also help to facilitate reimbursement of these therapies. Disclosure of Interests Anne Musters: None declared, Marjolijne Kleijn-de Graaf: None declared, Sander Tas Consultant of: Gebro, GSK, AbbVie, Galvani, Arthrogen/MeiraGTx, Galapagos, Grant/research support from: Pfizer, GSK, Celgene, BMS, Sanofi, AstraZeneca